We are continuing the study of the immunopathogenesis of human digestive tract cancer by conducting integrated clinical, pathological and immunochemical studies. We will study (1) the pathophysiology and metabolism of CEA, essential for basic understanding of the clinical application of CEA (and of other tumor markers) in benign and malignant clinical states; (2) the role of the liver in the metabolism and excretion of CEA. CEA and other antigens produced by primary sites as well as by metastases to the liver are detectable in the secretions of liver, biliary tract, pancreas and duodenal juice. We will continue to identify and characterize immunochemically CEA, CEA-like and other tumor associated substances in these fluids, compare them with primary and metastatic tumor sources, and to develop assays for use in assessing their clinical use. (3) Malignant ascites and pleural effusions provide large volumes of autologous human cancer cells growing "in vivo" and producing high concentrations of CEA, alphafetoprotein, and other macromolecules characteristic of malignancy. We will compare extravascular sources of CEA and other tumor markers with the primary tissue source, characterize them immunochemically, develop assays for them: (a) as a means for improving the detection of malignancy in effusions, (b) for identifying the primary tissue source, and (c) to evaluate their use in monitoring therapy. (4) We will utilize the fluids as a source for new tumor markers, and (5) elucidate the mechanisms of the formation of malignant effusions.